Understanding and re-engineering adenovirus late gene expression: controlling the gatekeeper to productive infection. (360G-Wellcome-094713_Z_10_Z)
Two proteins encoded within the adenovirus major late transcription unit (MLTU; a large gene that encodes the viral structural proteins), L4-22K and L4-33K, are not themselves part of virus particles but are required for production of particle proteins from the MLTU. Moreover, although the L4-22K and L4-33K genes lie within the MLTU, they are initially expressed from an independent promoter, which is crucial for infection to progress to the production of progeny. We therefore propose here to re- engineer this promoter, to prevent its activation during infection and place it under artificial control. A vector carrying this altered promoter will produce structural proteins and progeny particles in cell culture in the presence of inducer but will be unable to do either of these things when used in vivo. The specific objectives of the proposal are: To characterise the adenovirus L4 promoter, its key cis-acting elements and their response to transcription factors. To engineer the aden ovirus L4 promoter to eliminate its response to known activators and to make it inducible in appropriate cells in culture: To construct and validate an adenovirus E1-deleted vector containing the engineered promoter.
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Grant Details
Amount Awarded | 229258 |
Applicant Surname | Leppard |
Approval Committee | Molecules, Genes and Cells Funding Committee |
Award Date | 2011-03-09T00:00:00+00:00 |
Financial Year | 2010/11 |
Grant Programme: Title | Project Grant |
Internal ID | 094713/Z/10/Z |
Lead Applicant | Dr Keith Leppard |
Partnership Value | 229258 |
Planned Dates: End Date | 2014-12-18T00:00:00+00:00 |
Planned Dates: Start Date | 2011-09-19T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | West Midlands |